RESUMO
Lower HMW (high molecular weight) adiponectin levels are associated with obesity, insulin resistance, and metabolic syndrome in children and adolescents. However, data on HMW levels in pediatric population with hypertension are lacking. This study aimed to examine the association and predictive capacity of HMW levels, HMW/HOMA-IR, and HMW/APN ratio with hypertension in obese children and adolescents. The 299 pediatric subjects were grouped in obese hypertensive (OH), obese normotensive (ON), and normal weight normotensive (NN). Plasma concentrations of HMW were investigated by ELISA. ANOVA was used to compare study groups, and a binary logistic regression analysis was used to verify if HMW, HMW/HOMA-IR, HMW/APN, APN, APN/HOMA-IR, and HOMA-IR are associated to hypertension regardless obesity in children and adolescents. To compare the strength and performance of each biomarker to classify individuals with and without hypertension, the receiver-operating characteristic (ROC) curve, area under the curve (AUC), and Youden index (J) were evaluated. Both HMW plasma levels and the HMW/HOMA-IR ratio were significantly lower in the OH group when compared to the ON group (HMW: 2.00 ± 1.33 µg/mL vs 2.48 ± 1.48 µg/mL; HMW/HOMA-IR ratio: 0.87 ± 0.95 vs 1.27 ± 1.2; P < 0.05) and NN weight groups (HMW: 2.00 ± 1.33 µg/mL vs 4.02 ± 1.99 µg/mL; HMW/HOMA-IR ratio: 0.87 ± 0.95 vs 2.62 ± 1.86; P < 0.05). Hypertension was associated with lowest HMW (OR = 4.50; 95% CI = 1.41-15.84) and HMW/HOMA-IR (OR = 12.13; 95% CI = 2.51-92.93) regardless of obesity. However, HOMA-IR or the HMW/APN was not significant (P > 0.05). In the ROC curve analyses, the HMW and HMW/HOM-IR were more sensitive to detect hypertension in children and adolescents with obesity. Conclusion: Low levels of HMW oligomer and HMW/HOM-IR are associated with hypertension in childhood obesity. Thus, these biomarkers could be clinically useful in identifying hypertension in childhood obesity. What is Known: ⢠HMW has previously been reported as the most biologically active isoform of adiponectin, and lower HMW concentrations are associated with obesity, insulin resistance, and metabolic syndrome in children and adolescents. ⢠HMW/HOMA-IR ratio is a sensitive predictor for metabolic syndrome in adults. What is New: ⢠HMW levels are associated with hypertension in children and adolescents, independently of presence of obesity. ⢠HMW was more sensitive to detect hypertension in children and adolescents with obesity when compared to HMW/HOMA-IR, HMW/APN, APN, APN/HOMA-IR, or HOMA-IR.
Assuntos
Hipertensão , Resistência à Insulina , Síndrome Metabólica , Obesidade Infantil , Adulto , Adolescente , Criança , Humanos , Obesidade Infantil/complicações , Síndrome Metabólica/complicações , Síndrome Metabólica/diagnóstico , Adiponectina , Peso Molecular , Biomarcadores , Hipertensão/complicações , Hipertensão/diagnósticoRESUMO
High molecular weight PAHs (HMW PAHs) are dangerous pollutants widely distributed in the environment. The use of microorganisms represents an important tool for HMW PAHs bioremediation, so, the understanding of their biochemical pathways facilitates the development of biodegradation strategies. For this reason, the potential role of species of microalgae, bacteria, and microalga-bacteria consortia in the degradation of HMW PAHs is discussed. The identification of their metabolites, mostly by GC-MS and LC-MS, allows a better approach to the enzymes involved in the key steps of the metabolic pathways of HMW PAHs biodegradation. So, this review intends to address the proteomic research on enzyme activities and their involvement in regulating essential biochemical functions that help bacteria and microalgae in the biodegradation processes of HMW PAHs. It is noteworthy that, given that to the best of our knowledge, this is the first review focused on the mass spectrometry identification of the HMW PAHs metabolites; whereby and due to the great concern of the presence of HMW PAHs in the environment, this material could help the urgency of developing new bioremediation methods. The elucidation of the metabolic pathways of persistent pollutant degrading microorganisms should lead to a better knowledge of the enzymes involved, which could contribute to a very ecological route to the control of environmental contamination in the future.
Assuntos
Microalgas , Hidrocarbonetos Policíclicos Aromáticos , Bactérias , Biodegradação Ambiental , Espectrometria de Massas , Peso Molecular , ProteômicaRESUMO
In this work, previously synthesized and characterized core-shell silica nanoparticles (FCSNP) functionalized with immobilized molecular bait, Cibacron blue, and a porous polymeric bis-acrylamide shell were incubated with pooled urine samples from adult women or men with normal weight, overweight or obesity for the isolation of potential biomarkers. A total of 30 individuals (15 woman and 15 men) were included. FCSNP allowed the capture of a variety of low molecular weight (LMW) proteins as evidenced by mass spectrometry (MS) and the exclusion of high molecular weight (HMW) proteins (>34 kDa) as demonstrated by SDS-PAGE and 2D SDS-PAGE. A total of 36 proteins were successfully identified by MS and homology database searching against the Homo sapiens subset of the Swiss-Prot database. Identified proteins were grouped into different clusters according to their abundance patterns. Four proteins were found only in women and five only in men, whereas 27 proteins were in urine from both genders with different abundance patterns. Based on these results, this new approach represents an alternative tool for isolation and identification of urinary biomarkers.
Assuntos
Obesidade/urina , Proteinúria/urina , Proteômica , Adulto , Biomarcadores/urina , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: A major drawback in Alzheimer's disease (AD) is the lack of validated biomarkers for routine clinical diagnostic. We have reported earlier a novel blood biomarker, named Alz-tau®, based on variants of platelet tau. This marker evaluates the ratio of high molecular weight tau (HMWtau) and the low molecular weight (LMWtau) tau. OBJECTIVE: To analyze a potential novel source of antigen for Alz-tau®, plasma tau, detected by immunoreactivity with the novel monoclonal antibody, tau51. METHODS: We evaluated tau variants in plasma precipitated with ammonium sulfate from 36 AD patients and 15 control subjects by western blot with this novel monoclonal antibody. RESULTS: The HMW/LMWtau ratio was statistically different between AD patients and controls. CONCLUSIONS: Plasma tau variants are suitable to be considered as a novel antigen source for the Alz-tau® biomarker for AD.
Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico , Anticorpos Monoclonais/sangue , Variação Genética/fisiologia , Proteínas tau/sangue , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/genética , Anticorpos Monoclonais/genética , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas tau/genéticaRESUMO
Next-generation genome mapping through nanochannels (Bionano optical mapping) of plant genomes brings genome assemblies to the 'nearly-finished' level for reliable and detailed gene annotations and assessment of structural variations. Despite the recent progress in its development, researchers face the technical challenges of obtaining sufficient high molecular weight (HMW) nuclear DNA due to cell walls which are difficult to disrupt and to the presence of cytoplasmic polyphenols and polysaccharides that co-precipitate or are covalently bound to DNA and might cause oxidation and/or affect the access of nicking enzymes to DNA, preventing downstream applications. Here we describe important improvements for obtaining HMW DNA that we tested on Solanum crops and wild relatives. The methods that we further elaborated and refined focus on â¢Improving flexibility of using different tissues as source materials, like fast-growing root tips and young leaves from seedlings or in vitro plantlets.â¢Obtaining nuclei suspensions through either lab homogenizers or by chopping.â¢Increasing flow sorting efficiency using DAPI (4',6-diamidino-2-phenylindole) and PI (propidium iodide) DNA stains, with different lasers (UV or 488â¯nm) and sorting platforms such as the FACSAria and FACSVantage flow sorters, thus making it appropriate for more laboratories working on plant genomics. The obtained nuclei are embedded into agarose plugs for processing and isolating uncontaminated HMW DNA, which is a prerequisite for nanochannel-based next-generation optical mapping strategies.
RESUMO
Endocrine resistance may develop as a consequence of enhanced growth factor signaling. Fibroblast growth factor 2 (FGF2) consists of a low and several high molecular weight forms (HMW-FGF2). We previously demonstrated that antiprogestin-resistant mammary carcinomas display lower levels of progesterone receptor A isoforms (PRA) than B isoforms (PRB). Our aim was to evaluate the role of FGF2 isoforms in breast cancer progression. We evaluated FGF2 expression, cell proliferation, and pathway activation in models with different PRA/PRB ratios. We performed lentiviral infections of different FGF2 isoforms using the human hormone-responsive T47D-YA cells, engineered to only express PRA, and evaluated tumor growth, metastatic dissemination, and endocrine responsiveness. We assessed FGF2 expression and localization in 81 human breast cancer samples. Antiprogestin-resistant experimental mammary carcinomas with low PRA/PRB ratios and T47D-YB cells, which only express PRB, displayed higher levels of HMW-FGF2 than responsive variants. HMW-FGF2 overexpression in T47D-YA cells induced increased tumor growth, lung metastasis, and antiprogestin resistance compared to control tumors. In human breast carcinomas categorized by their PRA/PRB ratio, we found nuclear FGF2 expression in 55.6% of tumor cells. No differences were found between nuclear FGF2 expression and Ki67 proliferation index, tumor stage, or tumor grade. In low-grade tumor samples, moderate to high nuclear FGF2 levels were associated to carcinomas with low PRA/PRB ratio. In conclusion, we show that HMW-FGF2 isoforms are PRB targets which confer endocrine resistance and are localized in the nuclei of breast cancer samples. Hence, targeting intracellular FGF2 may contribute to overcome tumor progression.
Assuntos
Neoplasias da Mama/genética , Fator 2 de Crescimento de Fibroblastos/metabolismo , Animais , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Peso MolecularRESUMO
OBJECTIVE: This study was to investigate whether the metabolic abnormalities of adipokines and asymmetrical dimethylarginine (ADMA) associate with pulmonary function deficits in adolescents with obesity and asthma. METHODS: This study enrolled 28 obese adolescents with asthma, 46 obese adolescents without asthma, 58 normal-weight adolescents with asthma, and 63 healthy control subjects. Serum levels of leptin, high-molecule-weight (HMW) adiponectin, retinol binding protein 4 (RBP4), asymmetrical dimethylarginine (ADMA), and pulmonary function were qualified. RESULTS: The obese subjects had higher levels of leptin and ADMA but lower levels of HMW adiponectin than the normal-weight subjects with or without asthma. The subjects with asthma had higher levels of RBP4 than those without asthma. The obese adolescents with asthma had lowest forced expiratory lung volume in the first second (FEV1)/forced vital capacity (FVC) ratio among the four study groups. In all the study subjects and in the subjects with asthma alone, the FEV1/FVC ratio associated negatively with leptin, however, such association was rendered non-significant when adjusted for BMI. The pulmonary function deficits associated inversely with BMI percentile in the subjects with asthma. However, the decreased FEV1/FVC ratio was not correlated with HMW adiponectin, RBP4 or ADMA. CONCLUSIONS: Our present study confirmed obstructive pattern of pulmonary function characterized by the reduced FEV1/FVC ratio in the obese adolescents with asthma. These pulmonary deficits were associated inversely with the increased BMI percentile.
Assuntos
Adipocinas/metabolismo , Arginina/análogos & derivados , Asma/epidemiologia , Asma/fisiopatologia , Obesidade Infantil/epidemiologia , Obesidade Infantil/fisiopatologia , Adiponectina/metabolismo , Adolescente , Arginina/metabolismo , Criança , Feminino , Humanos , Leptina/metabolismo , Pulmão/fisiopatologia , Masculino , Testes de Função Respiratória , Proteínas Plasmáticas de Ligação ao Retinol/metabolismoRESUMO
Background The quality of wheat grain depends on several characteristics, among which the composition of high molecular weight glutenin subunits, encoded by Glu-1 loci, are the most important. Application of biotechnological tools to accelerate the attainment of homozygous lines may influence the proportion of segregated genotypes. The objective was to determine, whether the selection pressure generated by the methods based on in vitro cultures, may cause a loss of genotypes with desirable Glu-1 alleles. Results Homozygous lines were derived from six winter wheat crosses by pollination with maize (DH-MP), anther culture (DH-AC) and single seed descent (SSD) technique. Androgenetically-derived plants that originated from the same callus were examined before chromosome doubling using allele-specific and microsatellite markers. It was found that segregation distortion in SSD and DH-MP populations occurred only in one case, whereas in anther-derived lines they were observed in five out of six analyzed combinations. Conclusions Segregation distortion in DH-AC populations was caused by the development of more than one plant of the same genotype from one callus. This distortion was minimized if only one plant per callus was included in the population. Selection of haploid wheat plants before chromosome doubling based on allele-specific markers allows us to choose genotypes that possess desirable Glu-1 alleles and to reduce the number of plants in the next steps of DH production. The SSD technique appeared to be the most advantageous in terms of Mendelian segregation, thus the occurrence of residual heterozygosity can be minimized by continuous selfing beyond the F6 generation.
Assuntos
Triticum/genética , Segregação de Cromossomos , Sementes/genética , Técnicas In Vitro , Repetições de Microssatélites , Zea mays , Alelos , Genótipo , Glutens/análise , HomozigotoRESUMO
OBJECTIVE: To examine associations of urinary phthalate levels with blood pressure (BP) and serum triglyceride and lipoprotein levels in children. STUDY DESIGN: We performed a cross-sectional analysis of a subsample of US children aged 6-19 years who participated in the National Health and Nutrition Examination Survey between 2003 and 2008. We quantified exposure to 3 families of phthalates--low molecular weight, high molecular weight and di-2-ethylhexylphthalate (DEHP)--based on molar concentration of urinary metabolites. We assessed descriptive, bivariate, and multivariate associations with BP and lipid levels. RESULTS: Controlling for an array of sociodemographic and behavioral factors, as well as diet and body mass index, levels of metabolites of DEHP, a phthalate commonly found in processed foods, were associated with higher age-, sex-, and height-standardized BP. For each log unit (roughly 3-fold) increase in DEHP metabolites, a 0.041 SD unit increase in systolic BP z-score was identified (P = .047). Metabolites of low molecular weight phthalates commonly found in cosmetics and personal care products were not associated with BP. Phthalate metabolites were not associated with triglyceride levels, high-density lipoprotein level, or prehypertension. CONCLUSIONS: Dietary phthalate exposure is associated with higher systolic BP in children and adolescents. Further work is needed to confirm these associations, as well as to evaluate opportunities for intervention.
Assuntos
Exposição Ambiental/efeitos adversos , Poluentes Ambientais/efeitos adversos , Hipertensão/induzido quimicamente , Ácidos Ftálicos/efeitos adversos , Pré-Hipertensão/induzido quimicamente , Adolescente , Biomarcadores/sangue , Biomarcadores/urina , Criança , Estudos Transversais , Dislipidemias/induzido quimicamente , Exposição Ambiental/análise , Monitoramento Ambiental , Poluentes Ambientais/urina , Feminino , Humanos , Hipertensão/sangue , Hipertensão/urina , Modelos Lineares , Lipoproteínas HDL/sangue , Modelos Logísticos , Masculino , Análise Multivariada , Inquéritos Nutricionais , Ácidos Ftálicos/urina , Pré-Hipertensão/sangue , Pré-Hipertensão/urina , Triglicerídeos/sangue , Estados Unidos , Adulto JovemRESUMO
Plasma adiponectin and the coding gene for adiponectin, ADIPOQ, are thought to explain part of the interaction between obesity, insulin resistance, type 2 diabetes (T2DM) and coronary artery disease (CAD). Here, we illustrate the role that adiponectin and ADIPOQ variants might play in the modulation of CAD, especially in the occurrence of hyperglycemia. Recent evidence suggests that total and high molecular weight (HMW) adiponectin levels are apparent markers of better cardiovascular prognosis in patients with low risk of CAD. However, in subjects with established or high risk of CAD, these levels are associated with poorer prognosis. We also provide recent evidences relating to the genetic control of total and HMW adiponectin levels, especially evidence regarding ADIPOQ. Accumulated data suggest that both adiponectin levels and polymorphisms in the ADIPOQ gene are linked to the risk of CAD in patients with hyperglycemia, and that these associations seem to be independent from each other, even if adiponectin levels are partly dependent on ADIPOQ.
Os níveis plasmáticos de adiponectina e o gene codante desta proteína, ADIPOQ, parecem explicar parte da interação de doenças como obesidade, resistência à insulina, diabetes melito tipo 2 (DM2) e doença arterial coronariana (DAC). Apresentamos as evidências do papel tanto dos níveis de adiponectina quanto das variantes no ADIPOQ na modulação da DAC, sobretudo na presença de hiperglicemia. Estudos recentes sugerem que níveis de adiponectina total e de alto peso molecular (HMW) são marcadores de bom prognóstico DAC, sobretudo em pacientes de baixo risco cardiovascular, enquanto nos pacientes de alto risco ou com doença já estabelecida podem se associar com pior prognóstico. Apresentamos também as evidências em relação ao possível controle genético dos níveis circulantes de adiponectina, tanto total quanto da isoforma de alto peso molecular, sobretudo em relação ao ADIPOQ. A análise global dos dados sugere que tanto os níveis circulantes de adiponectina quanto polimorfismos no gene ADIPOQ estão implicados na evolução de DAC em pacientes com hiperglicemia e que essas associações podem existir de forma independente.